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Synlett
DOI: 10.1055/a-2602-6899
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Small Molecules in Medicinal Chemistry

Synthesis of 5-Functionalized 1-(Hetero)Aryl-1,2-thiazine 1-Oxides through a CSIC Reaction Strategy

Yaroslav O. Chuchvera
a   Enamine Ltd., Winston Churchill Street 78, Kyiv 02094, Ukraine
b   Taras Shevchenko National University of Kyiv, Volodymyrska Steet 60, Kyiv 01033, Ukraine
,
Oleksandr P. Korobka
a   Enamine Ltd., Winston Churchill Street 78, Kyiv 02094, Ukraine
c   V.N. Karazin Kharkiv National University, Svobody Square 4, Kharkiv 61022, Ukraine
,
Yurii O. Horbatochkin
a   Enamine Ltd., Winston Churchill Street 78, Kyiv 02094, Ukraine
c   V.N. Karazin Kharkiv National University, Svobody Square 4, Kharkiv 61022, Ukraine
,
Eugeniy N. Ostapchuk
a   Enamine Ltd., Winston Churchill Street 78, Kyiv 02094, Ukraine
b   Taras Shevchenko National University of Kyiv, Volodymyrska Steet 60, Kyiv 01033, Ukraine
,
Maria V. Popova
b   Taras Shevchenko National University of Kyiv, Volodymyrska Steet 60, Kyiv 01033, Ukraine
d   Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany
,
Svitlana V. Shishkina
e   Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska Street 5, Kyiv 02094, Ukraine
f   SSI ‘Institute for Single Crystals’, National Academy of Sciences of Ukraine, Nauky Avenue 60, Kharkiv 61001, Ukraine
,
Yulian M. Volovenko
b   Taras Shevchenko National University of Kyiv, Volodymyrska Steet 60, Kyiv 01033, Ukraine
,
Alexey V. Dobrydnev  ∗
a   Enamine Ltd., Winston Churchill Street 78, Kyiv 02094, Ukraine
b   Taras Shevchenko National University of Kyiv, Volodymyrska Steet 60, Kyiv 01033, Ukraine
› Author Affiliations
This work was funded by Enamine Ltd. Additional funding from the Ministry of Education and Science of Ukraine is also acknowledged.
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Dedicated to Prof. José Marco-Contelles for his invaluable contribution to the CSIC reaction.

Abstract

Herein, we report an efficient strategy for the synthesis of C5-functionalized 1-(hetero)aryl-1,2-thiazine 1-oxides (i.e., C5-functionalized six-membered endocyclic sulfoximines) based on the carbanion-mediated sulfonate (or sulfonamide) intermolecular coupling and intramolecular cyclization (CSIC) reaction. The starting compounds are readily available 2,2-disubstituted 3-bromopropanenitriles and imino(methyl)(hetero/aryl)-λ6-sulfanones, and the reaction is performed in a one-pot fashion. The method works well and provides previously unreported spirocyclic and S-heteroaryl-substituted 1,2-thiazine 1-oxides. These compounds are designed as multi-target small molecules and a preliminary in silico study indicates their good binding affinity to CLK4 and MAO B – the receptors associated with cancer and neurodegenerative diseases.

Key words

sulfoximines - CSIC reaction - cyclization - alkylation - enamines

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2602-6899.
  • Supporting Information


Publication History

Received: 28 February 2025

Accepted after revision: 07 May 2025

Accepted Manuscript online:
07 May 2025

Article published online:
18 June 2025

© 2025. Thieme. All rights reserved

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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